This invention relates to a process for the preparation of 1.alpha.,25S,26-trihydroxycholecalciferol and the analog 1.alpha.,25R,26-trihydroxycholecalciferol and the use thereof by treatment of disease states characterized by higher than normal serum levels of 1,25(OH).sub.2 D.sub.3.
Vitamin D.sub.3 is a well-known agent for the control of calcium and phosphorous homeostasis. In the normal animal or human, this compound is known to stimulate intestinal calcium transport and bone-calcium mobilization and is effective in preventing rickets.
It is also now well known that to be effective, vitamin D.sub.3 must be converted in vivo to its hydroxylated forms. For example, the vitamin is first hydroxylated in the liver to form 25-hydroxy-vitamin D.sub.3 and is further hydroxylated in the kidney to produce 1.alpha.,25-dihydroxy vitamin D.sub.3 or 24,25-dihydroxy vitamin D.sub.3. The 1.alpha.,25-dihydroxylated form of the vitamin is generally considered to be the physiologically-active or hormonal form of the vitamin and to be responsible for what are termed the vitamin D-like activities such as increasing intestinal absorption of calcium and phosphate, mobilizing bone mineral and retaining calcium in the kidneys.
Since the discovery of biologically-active metabolites of vitamin D.sub.3, there has been much interest in the preparation of structural analogs of these metabolites because such compounds may represent useful therapeutic agents for the treatment of diseases resulting from calcium metabolism disorders. Specifically included among the disease states for which the compound of formula I is indicated are hypercalcemia, sarcoidosis, hypercalciuria, nephrolithiasis, nephrocalcinosis and other disease states which are characterized by higher-than-normal levels of the active vitamin D.sub.3 metabolite, 1.alpha.,25-dihydroxycholecalciferol. The R and S epimers of 1,25,26-trihydroxycholecalciferol lower the serum level of 1,25-dihydroxycholecalciferol. Both the R and S epimers promote bone mineralization in vitamin D-deficient animals. The R epimer promotes bone mineralization in disodium-ethane-1-hydroxy-1,1-diphosphonate-blocked animals.